Notes on research into some aspects of stall-warning devices

The problems of detecting and indicating an approaching stall have been investigated in flight on an “Anson” aircraft. A lower-surface flap near the leading-edge of the wing detects the approaching stall at a speed which depends critically on the length of the flap and on its location, but the margin of warning speed over stalling-speed is reasonably independent of landing-flap position and throttle setting. Continues

A Personalized System for Conversational Recommendations

Searching for and making decisions about information is becoming increasingly difficult as the amount of information and number of choices increases. Recommendation systems help users find items of interest of a particular type, such as movies or restaurants, but are still somewhat awkward to use. Our solution is to take advantage of the complementary strengths of personalized recommendation systems and dialogue systems, creating personalized aides. We present a system -- the Adaptive Place Advisor -- that treats item selection as an interactive, conversational process, with the program inquiring about item attributes and the user responding. Individual, long-term user preferences are unobtrusively obtained in the course of normal recommendation dialogues and used to direct future conversations with the same user. We present a novel user model that influences both item search and the questions asked during a conversation. We demonstrate the effectiveness of our system in significantly reducing the time and number of interactions required to find a satisfactory item, as compared to a control group of users interacting with a non-adaptive version of the system

Erythema nodosum as a result of estrogen patch therapy for prostate cancer: a case report.

© 2015 Coyle et al.Introduction: Erythema nodosum is often associated with a distressing symptomatology, including painful subcutaneous nodules, polyarthropathy, and significant fatigue. Whilst it is a well-documented side-effect of estrogen therapy in females, we describe what we believe to be the first report in the literature of erythema nodosum as a result of estrogen therapy in a male. Case presentation: A 64-year-old Afro-Caribbean man with locally advanced carcinoma of the prostate agreed to participate in a randomized controlled trial comparing estrogen patches with luteinizing hormone-releasing hormone analogs to achieve androgen deprivation, and was allocated to the group receiving estrogen patches. One month later he presented with tender lesions on his shins and painful swelling of his ankles, wrists, and left shoulder. This was followed by progressive severe fatigue that required hospital admission, where he was diagnosed with erythema nodosum by a rheumatologist. Two months after discontinuing the estrogen patches the erythema nodosum, and associated symptoms, had fully resolved, and to date he remains well with no further recurrence. Conclusion: Trial results may establish transdermal estrogen as an alternative to luteinizing hormone-releasing hormone analogs in the management of prostate cancer, and has already been established as a therapy for male to female transsexuals. It is essential to record the toxicity profile of transdermal estrogen in men to ensure accurate safety information. This case report highlights a previously undocumented toxicity of estrogen therapy in men, of which oncologists, urologists, and endocrinologists need to be aware. Rheumatologists and dermatologists should add estrogen therapy to their differential diagnosis of men presenting with erythema nodosum

Sunlit Uplands: The Genius of the NICE Reference Case

The NICE reference case has received widespread acceptance in health technology assessment. The lifetime cost-per-QALY model and constructed claims for product impact have been widely emulated in country-specific guidelines for formulary submission as well as in publications in the leading health technology journals. Unfortunately, from the perspective of the standards of normal science, adherence to the reference case standard means that the claims made are typically non-evaluable. They have to be taken at face value. They may suggest potential evaluable hypotheses for clinical and cost-effectiveness claims, but there is no requirement in the reference case for claims to be put in an evaluable form and for manufacturers to suggest possible protocols for product impact assessment. This is not an acceptable situation. Absent the standards for falsification and replication, which are at the core of the scientific method, we have no idea whether the claims accepted by NICE are right or even if they are wrong. If we accept the reference case paradigm should we conclude that the sunlit uplands of formulary decisions based on non-evaluable simulated claims for cost-effectiveness has been reached? Have we rejected natural selection in favor of intelligent design? Conflict of Interest None Type: Commentar

Great Expectations: Cost-Utility Models as Decision Criteria

One of the more puzzling features of published claims for cost-effectiveness is the popularity of claims presented in terms of quality adjusted life years (QALYs). Despite the popularity of QALYs as the ‘gold standard’ outcome measures among academic audiences, professional groups and a number of single payer health care systems, there is no evidence to suggest that cost-per-QALY based claims have ever been assessed, either through experimentation or observation, to support formulary decisions. In part this stems from the fact that cost-per-QALY claims are typically not expressed in evaluable terms; it also stems from the fact that, despite the plethora of QALY publications, QALYs are not collected on a regular basis by any health care system as part of administrative claims or electronic medical records. In the US QALYs have typically been ignored by health care decision makers. Given this, the continuing popularity of utility-based measures for studies published in the leading pharmacoeconomics journals is difficult to understand. One possible explanation is that those promoting QALY claims are locked into a relativist position that defends the publication of nontestable product claims. A position that is reinforced by recommendations from ‘peer organizations’ such as the Academy of Managed Care Pharmacy (AMCP) in their promotion of their Format for Formulary Submission standards which support the role of lifetime cost-per-QALY modeled imaginary worlds or thought experiments. Another explanation is that QALYs have been taken at face value with little though given to how they might be implemented to support both initial formulary decisions as well as ongoing disease area therapeutic class reviews. The purpose of this review is to put the case that the continued emphasis on cost-per-QALY claims has no practical benefit in formulary decision making.   Type: Commentar

Another Imaginary World: The ICER Claims for the Long-Term Cost-Effectiveness and Pricing of Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors in Tardive Dyskinesia

The recently released value assessment of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia by the Institute for Clinical and Economic Review (ICER) relies upon a long-term modeling exercise to support recommendations for what the ICER sees as the appropriate pricing for these products if prices are to be judged ‘cost-effective’. In this case, the recommendations are for a substantive price reduction of some 90% over WAC. Needless to say, this recommendation is unlikely to be welcomed with open arms by the respective manufacturers of valbenazine and deutetrabenazine. Unfortunately, as has been argued in a number of commentaries published over the past 18 months in INNOVATIONS in Pharmacy, the ICER endorsed health technology assessment methodology that underpins this exercise in building a modeled imaginary world to justify product pricing recommendations is fatally flawed: it does not meet the standards of normal science. Rather than addressing the issue of claims validation for VMAT2 products, the question of generating modeled evaluable claims, among others, for clinical, quality of life and resource utilization outcomes, the analysis focuses on claims that are neither credible nor evaluable and, of course, non-replicable. A more positive and useful approach would be for ICER to focus on a framework where claims could be assessed in the short term to provide feedback to health system decision makers, physicians and patients. Instead, we are asked to believe that we can model 20 or 30 years into the future to establish non-evaluable claims for pricing and, ultimately, access. Conflict of Interest: None   Type: Commentar

Imaginary Worlds and Efficiency Frontiers: Should We Abandon the IQWiG Health Technology Assessment Model?

The contribution of cost-effectiveness analysis to the pricing of pharmaceuticals in Germany is at best marginal and in many, if not most cases, absent. While this may reflect a reasonable belief that cost-effectiveness analysis adds little if anything to pricing and formulary placement decisions, its marginalization reflects considerable dissatisfaction, if not frustration, with modeling efforts by the Institut für Qualität und Wirtschaftlichkeit im Gesundheitseesen (IQWiG). In part, this reflects the rejection of quality adjusted life years (QALYs) as the common outcome standard, together with the adoption of the efficiency frontier as the default framework for modeled claims. The purpose of this commentary is to consider the merits, in the German context, of an efficiency frontier framework for cost-effectiveness and pricing decisions. The commentary concludes that the efficiency frontier framework for health technology assessment, in supporting the creation of non-evaluable claims from models or simulations, fails of to meet the standards of normal science: it fails to support claims that are credible, evaluable and replicable. It should be abandoned. If cost-effectiveness modeling is to play a constructive role in pricing negotiations in Germany then manufacturers should be required to submit evaluable claims. The most effective way of ensuring this is to require manufacturers to accompany any submission for a new product with a protocol detailing how their claims, to include those for clinical outcomes, cost-effectiveness and budget impact, are to be evaluated and reported to decision makers in a meaningful time frame.   Type: Commentar

Expression of the neural cell adhesion molecule NCAM in endocrine cells

We examined the expression of the neural cell adhesion molecule NCAM in a number of endocrine tissues of adult rat and in an endocrine tumor cell line. NCAM was found by immunoelectron microscopy to be present on the surface of all endocrine cells in the three lobes of the hypophysis, although staining was relatively less intense in the intermediate lobe, and in pancreatic islets. Pituicytes, hypophyseal glial cells, were also labeled for NCAM. A rat insulinoma cell line (RIN A2) also expressed NCAM as judged by immunocytochemistry. Analysis of NCAM antigenic determinants (Mr 180, 140, and 120 KD) revealed large variations in the relative proportions of NCAM polypeptides present in the different tissues. Although all tissues and cell lines expressed NCAM-140, NCAM-180 was not detected in the adenohypophysis, pancreas, or adrenal medulla, and NCAM-120 was found in none of the endocrine tissues or cell lines except at low levels in the neurohypophysis. The tumor cell line expressed significant levels of NCAM-180, which was most abundant in the neurohypophysis. These results show that NCAM expression appears to be a general property of endocrine cells, although the antigenic composition differs markedly from that in brain tissue. These data are discussed with regard to the embryological origins of the different endocrine tissues, and possible functional implications are suggested